Search

Your search keyword '"Burgering, Boudewijn M T"' showing total 266 results
Start Over Author "Burgering, Boudewijn M T"
266 results on '"Burgering, Boudewijn M T"'

5. Direct detection of 8-oxo-dG using nanopore sequencing

Author

Pagès-Gallego, Marc, primary, van Soest, Daan M. K., additional, Besselink, Nicolle J. M., additional, Straver, Roy, additional, Keijer, Janneke P., additional, Vermeulen, Carlo, additional, Marcozzi, Alessio, additional, van Roosmalen, Markus J., additional, van Boxtel, Ruben, additional, Burgering, Boudewijn M. T., additional, Dansen, Tobias B., additional, and de Ridder, Jeroen, additional

Published
2024
Full Text
View/download PDF

6. ALS-associated C21ORF2 variant disrupts DNA damage repair, mitochondrial metabolism, neuronal excitability and NEK1 levels in human motor neurons

Author

Brain, TN groep Pasterkamp, CMM Groep Burgering, Cancer, TN groep Meye, The Neural Circuits Underlying Stress Eating, CMM Sectie Molecular Cancer Research, Neurogenetica, Genetic Risks, Neurologen, Projectafdeling ALS, Translational Neuroscience, Regenerative Medicine and Stem Cells, Zelina, Pavol, de Ruiter, Anna Aster, Kolsteeg, Christy, van Ginneken, Ilona, Vos, Harmjan R, Supiot, Laura F, Burgering, Boudewijn M T, Meye, Frank J, Veldink, Jan H, van den Berg, Leonard H, Pasterkamp, R Jeroen, Brain, TN groep Pasterkamp, CMM Groep Burgering, Cancer, TN groep Meye, The Neural Circuits Underlying Stress Eating, CMM Sectie Molecular Cancer Research, Neurogenetica, Genetic Risks, Neurologen, Projectafdeling ALS, Translational Neuroscience, Regenerative Medicine and Stem Cells, Zelina, Pavol, de Ruiter, Anna Aster, Kolsteeg, Christy, van Ginneken, Ilona, Vos, Harmjan R, Supiot, Laura F, Burgering, Boudewijn M T, Meye, Frank J, Veldink, Jan H, van den Berg, Leonard H, and Pasterkamp, R Jeroen

Published
2024

7. Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA.

Author

CMM Groep Dansen, Cancer, CMM Groep Kloosterman, CMM Groep De Keizer, CMM Groep Burgering, CMM Groep Cuppen, CMM Sectie Molecular Cancer Research, van Soest, Daan M K, Polderman, Paulien E, den Toom, Wytze T F, Keijer, Janneke P, van Roosmalen, Markus J, Leyten, Tim M F, Lehmann, Johannes, Zwakenberg, Susan, De Henau, Sasha, van Boxtel, Ruben, Burgering, Boudewijn M T, Dansen, Tobias B, CMM Groep Dansen, Cancer, CMM Groep Kloosterman, CMM Groep De Keizer, CMM Groep Burgering, CMM Groep Cuppen, CMM Sectie Molecular Cancer Research, van Soest, Daan M K, Polderman, Paulien E, den Toom, Wytze T F, Keijer, Janneke P, van Roosmalen, Markus J, Leyten, Tim M F, Lehmann, Johannes, Zwakenberg, Susan, De Henau, Sasha, van Boxtel, Ruben, Burgering, Boudewijn M T, and Dansen, Tobias B

Published
2024

9. Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA.

Author

van Soest, Daan M. K., Polderman, Paulien E., den Toom, Wytze T. F., Keijer, Janneke P., van Roosmalen, Markus J., Leyten, Tim M. F., Lehmann, Johannes, Zwakenberg, Susan, De Henau, Sasha, van Boxtel, Ruben, Burgering, Boudewijn M. T., and Dansen, Tobias B.

Subjects
NUCLEAR DNA, MITOCHONDRIA, CELL cycle, REACTIVE oxygen species, DNA damage
Abstract

Reactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of chromosomal DNA mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondria can directly damage nuclear DNA is largely lacking. In this study, we investigated the effects of H2O2 released by mitochondria or produced at the nucleosomes using a titratable chemogenetic approach. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2. Nuclear H2O2 gives rise to DNA damage and mutations and a subsequent p53 dependent cell cycle arrest. Mitochondrial H2O2 release shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. We conclude that H2O2 released from mitochondria is unlikely to directly damage nuclear genomic DNA, limiting its contribution to oncogenic transformation and aging. Nuclear DNA damage downstream of mitochondrial ROS is often cited to contribute to cancer initiation and aging. However, here the authors show that although H2O2 induces DNA mutations when produced near DNA, it does not when released by mitochondria. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

12. Pyruvate metabolism controls chromatin remodeling during CD4+ T cell activation

Author

CMM Groep Coffer, Cancer, Infection & Immunity, CMM Groep Burgering, CMM Groep Van Mil, CTI Radstake, CTI Research, Immuno/reuma onderzoek 3 (Loosdregt), Child Health, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Circulatory Health, CMM Sectie Molecular Cancer Research, CMM Sectie Stem Cells, Onderzoek, Regenerative Medicine and Stem Cells, Mocholi, Enric, Russo, Laura, Gopal, Keshav, Ramstead, Andrew G, Hochrein, Sophia M, Vos, Harmjan R, Geeven, Geert, Adegoke, Adeolu O, Hoekstra, Anna, van Es, Robert M, Pittol, Jose Ramos, Vastert, Sebastian, Rutter, Jared, Radstake, Timothy, van Loosdregt, Jorg, Berkers, Celia, Mokry, Michal, Anderson, Colin C, O'Connell, Ryan M, Vaeth, Martin, Ussher, John, Burgering, Boudewijn M T, Coffer, Paul J, CMM Groep Coffer, Cancer, Infection & Immunity, CMM Groep Burgering, CMM Groep Van Mil, CTI Radstake, CTI Research, Immuno/reuma onderzoek 3 (Loosdregt), Child Health, CDL Onderzoek Pasterkamp, Experimentele Afd. Cardiologie 1, Circulatory Health, CMM Sectie Molecular Cancer Research, CMM Sectie Stem Cells, Onderzoek, Regenerative Medicine and Stem Cells, Mocholi, Enric, Russo, Laura, Gopal, Keshav, Ramstead, Andrew G, Hochrein, Sophia M, Vos, Harmjan R, Geeven, Geert, Adegoke, Adeolu O, Hoekstra, Anna, van Es, Robert M, Pittol, Jose Ramos, Vastert, Sebastian, Rutter, Jared, Radstake, Timothy, van Loosdregt, Jorg, Berkers, Celia, Mokry, Michal, Anderson, Colin C, O'Connell, Ryan M, Vaeth, Martin, Ussher, John, Burgering, Boudewijn M T, and Coffer, Paul J

Published
2023

13. Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRASG12D glycolytic colorectal tumors

Author

Ludikhuize, Marlies C, Gevers, Sira, Nguyen, Nguyen T B, Meerlo, Maaike, Roudbari, S Khadijeh Shafiei, Gulersonmez, M Can, Stigter, Edwin C A, Drost, Jarno, Clevers, Hans, Burgering, Boudewijn M T, Rodríguez Colman, Maria J, Ludikhuize, Marlies C, Gevers, Sira, Nguyen, Nguyen T B, Meerlo, Maaike, Roudbari, S Khadijeh Shafiei, Gulersonmez, M Can, Stigter, Edwin C A, Drost, Jarno, Clevers, Hans, Burgering, Boudewijn M T, and Rodríguez Colman, Maria J

Abstract

Despite the fact that 5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC), the response rates in patients is limited to 50%. The mechanisms underlying 5-FU toxicity are debated, limiting the development of strategies to improve its efficacy. How fundamental aspects of cancer, such as driver mutations and phenotypic heterogeneity, relate to the 5-FU response remains obscure. This largely relies on the limited number of studies performed in pre-clinical models able to recapitulate the key features of CRC. Here, we analyzed the 5-FU response in patient-derived organoids that reproduce the different stages of CRC. We find that 5-FU induces pyrimidine imbalance, which leads to DNA damage and cell death in the actively proliferating cancer cells deficient in p53. Importantly, p53-deficiency leads to cell death due to impaired cell cycle arrest. Moreover, we find that targeting the Warburg effect in KRASG12D glycolytic tumor organoids enhances 5-FU toxicity by further altering the nucleotide pool and, importantly, without affecting non-transformed WT cells. Thus, p53 emerges as an important factor in determining the 5-FU response, and targeting cancer metabolism in combination with replication stress-inducing chemotherapies emerges as a promising strategy for CRC treatment.

Published
2022

14. FER regulates endosomal recycling and is a predictor for adjuvant taxane benefit in breast cancer

Author

Cancer, Pathologie Groep Derksen, CMM groep Liv, CMM Groep Lens, CMM Groep Burgering, CMM Groep Bos, CMM Sectie Molecular Cancer Research, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, Pathologie, Tavares, Sandra, Liv, Nalan, Pasolli, Milena, Opdam, Mark, Rätze, Max A K, Saornil, Manuel, Sluimer, Lilian M, Hengeveld, Rutger C C, van Es, Robert, van Werkhoven, Erik, Vos, Harmjan, Rehmann, Holger, Burgering, Boudewijn M T, Oosterkamp, Hendrika M, Lens, Susanne M A, Klumperman, Judith, Linn, Sabine C, Derksen, Patrick W B, Cancer, Pathologie Groep Derksen, CMM groep Liv, CMM Groep Lens, CMM Groep Burgering, CMM Groep Bos, CMM Sectie Molecular Cancer Research, CMM Sectie Celbiologie, Brain, Regenerative Medicine and Stem Cells, Pathologie, Tavares, Sandra, Liv, Nalan, Pasolli, Milena, Opdam, Mark, Rätze, Max A K, Saornil, Manuel, Sluimer, Lilian M, Hengeveld, Rutger C C, van Es, Robert, van Werkhoven, Erik, Vos, Harmjan, Rehmann, Holger, Burgering, Boudewijn M T, Oosterkamp, Hendrika M, Lens, Susanne M A, Klumperman, Judith, Linn, Sabine C, and Derksen, Patrick W B

Published
2022

16. FOXOs: masters of the equilibrium.

Author

Gui, Tianshu and Burgering, Boudewijn M. T.

Subjects
*ADP-ribosylation, *POST-translational modification, *CELL metabolism, *EQUILIBRIUM, *TRANSCRIPTION factors, *CELL proliferation, *CELLULAR signal transduction
Abstract

Forkhead box O (FOXO) transcription factors (TFs) are a subclass of the larger family of forkhead TFs. Mammalians express four members FOXO1, FOXO3, FOXO4, and FOXO6. The interest in FOXO function stems mostly from their observed role in determining lifespan, where in model organisms, increased FOXO activity results in extended lifespan. FOXOs act as downstream of several signaling pathway and are extensively regulated through post‐translational modifications. The transcriptional program activated by FOXOs in various cell types, organisms, and under various conditions has been described and has shed some light on what the critical transcriptional targets are in mediating FOXO function. At the cellular level, these studies have revealed a role for FOXOs in cell metabolism, cellular redox, cell proliferation, DNA repair, autophagy, and many more. The general picture that emerges hereof is that FOXOs act to preserve equilibrium, and they are important for cellular homeostasis. Here, we will first briefly summarize the general knowledge of FOXO regulation and possible functions. We will use genomic stability to illustrate how FOXOs ensure homeostasis. Genomic stability is critical for maintaining genetic integrity, and therefore preventing disease. However, genomic mutations need to occur during lifetime to enable evolution, yet their accumulation is believed to be causative to aging. Therefore, the role of FOXO in genomic stability may underlie its role in lifespan and aging. Finally, we will come up with questions on some of the unknowns in FOXO function, the answer(s) to which we believe will further our understanding of FOXO function and ultimately may help to understand lifespan and its consequences. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

19. Rewiring glucose metabolism improves 5-FU efficacy in p53-deficient/KRASG12D glycolytic colorectal tumors.

Author

Ludikhuize, Marlies C., Gevers, Sira, Nguyen, Nguyen T. B., Meerlo, Maaike, Roudbari, S. Khadijeh Shafiei, Gulersonmez, M. Can, Stigter, Edwin C. A., Drost, Jarno, Clevers, Hans, Burgering, Boudewijn M. T., and Rodríguez Colman, Maria J.

Subjects
COLON tumors, GLUCOSE metabolism, FLUOROURACIL, CANCER chemotherapy, GLYCOLYSIS, DNA damage, IRINOTECAN
Abstract

Despite the fact that 5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC), the response rates in patients is limited to 50%. The mechanisms underlying 5-FU toxicity are debated, limiting the development of strategies to improve its efficacy. How fundamental aspects of cancer, such as driver mutations and phenotypic heterogeneity, relate to the 5-FU response remains obscure. This largely relies on the limited number of studies performed in pre-clinical models able to recapitulate the key features of CRC. Here, we analyzed the 5-FU response in patient-derived organoids that reproduce the different stages of CRC. We find that 5-FU induces pyrimidine imbalance, which leads to DNA damage and cell death in the actively proliferating cancer cells deficient in p53. Importantly, p53-deficiency leads to cell death due to impaired cell cycle arrest. Moreover, we find that targeting the Warburg effect in KRASG12D glycolytic tumor organoids enhances 5-FU toxicity by further altering the nucleotide pool and, importantly, without affecting non-transformed WT cells. Thus, p53 emerges as an important factor in determining the 5-FU response, and targeting cancer metabolism in combination with replication stress-inducing chemotherapies emerges as a promising strategy for CRC treatment. In p53-deficient colorectal cancer organoids, 5-fluorouracil induces pyrimidine imbalance, which causes DNA damage and cell death. Rewiring glucose metabolism through PDK inhibition by DCA enhances 5-FU toxicity in glycolytic p53-deficient organoids. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

20. Berkchaetoazaphilone B has antimicrobial activity and affects energy metabolism

Author

MMB Research line 2, Infection & Immunity, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Ouyang, Xudong, Hoeksma, Jelmer, van der Velden, Gisela, Beenker, Wouter A G, van Triest, Maria H, Burgering, Boudewijn M T, den Hertog, Jeroen, MMB Research line 2, Infection & Immunity, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Ouyang, Xudong, Hoeksma, Jelmer, van der Velden, Gisela, Beenker, Wouter A G, van Triest, Maria H, Burgering, Boudewijn M T, and den Hertog, Jeroen

Published
2021

21. Implication of miR-126 and miR-139-5p in Plasmacytoid Dendritic Cell Dysregulation in Systemic Sclerosis

Author

Other research (not in main researchprogram), CMM Groep Burgering, Cancer, Infection & Immunity, CTI Van Loosdregt, DBG Metabole en Endocriene Ziekten, Lab Reumatologie/Klinische Immunologie, Translationele immunologie, CTI Meyaard, CTI Pandit, CMM Sectie Molecular Cancer Research, Chouri, Eleni, Wang, Maojie, Hillen, Maarten R, Angiolilli, Chiara, Silva-Cardoso, Sandra C, Wichers, Catharina G K, van der Kroef, Maarten, Bekker, Cornelis P J, Cossu, Marta, van Bon, Lenny, Affandi, Alsya J, Carvalheiro, Tiago, Pandit, Aridaman, van Roon, Joel A G, Beretta, Lorenzo, Burgering, Boudewijn M T, Radstake, Timothy R D J, Rossato, Marzia, Other research (not in main researchprogram), CMM Groep Burgering, Cancer, Infection & Immunity, CTI Van Loosdregt, DBG Metabole en Endocriene Ziekten, Lab Reumatologie/Klinische Immunologie, Translationele immunologie, CTI Meyaard, CTI Pandit, CMM Sectie Molecular Cancer Research, Chouri, Eleni, Wang, Maojie, Hillen, Maarten R, Angiolilli, Chiara, Silva-Cardoso, Sandra C, Wichers, Catharina G K, van der Kroef, Maarten, Bekker, Cornelis P J, Cossu, Marta, van Bon, Lenny, Affandi, Alsya J, Carvalheiro, Tiago, Pandit, Aridaman, van Roon, Joel A G, Beretta, Lorenzo, Burgering, Boudewijn M T, Radstake, Timothy R D J, and Rossato, Marzia

Published
2021

23. Interplay between metabolic identities in the intestinal crypt supports stem cell function

Author

Rodrguez-Colman, Maria J., Schewe, Matthias, Meerlo, Maaike, Stigter, Edwin, Gerrits, Johan, Pras-Raves, Mia, Sacchetti, Andrea, Hornsveld, Marten, Oost, Koen C., Snippert, Hugo J., Verhoeven-Duif, Nanda, Fodde, Riccardo, and Burgering, Boudewijn M. T.

Subjects
Intestines -- Physiological aspects, Physiological research, Stem cells -- Physiological aspects, Metabolism -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Maria J. Rodrguez-Colman [1]; Matthias Schewe [2]; Maaike Meerlo [1]; Edwin Stigter [1]; Johan Gerrits [3]; Mia Pras-Raves [3]; Andrea Sacchetti [2]; Marten Hornsveld [1]; Koen C. Oost [1]; [...]

Published
2017
Full Text
View/download PDF

26. Implication of miR-126 and miR-139-5p in Plasmacytoid Dendritic Cell Dysregulation in Systemic Sclerosis

Author

Chouri, Eleni, primary, Wang, Maojie, additional, Hillen, Maarten R., additional, Angiolilli, Chiara, additional, Silva-Cardoso, Sandra C., additional, Wichers, Catharina G. K., additional, van der Kroef, Maarten, additional, Bekker, Cornelis P. J., additional, Cossu, Marta, additional, van Bon, Lenny, additional, Affandi, Alsya J., additional, Carvalheiro, Tiago, additional, Pandit, Aridaman, additional, van Roon, Joel A. G., additional, Beretta, Lorenzo, additional, Burgering, Boudewijn M. T., additional, Radstake, Timothy R. D. J., additional, and Rossato, Marzia, additional

Published
2021
Full Text
View/download PDF

31. Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress

Author

Kops, Geert J. P. L., Dansen, Tobias B., Polderman, Paulien E., Saarloos, Ingrid, Wirtz, Karel W. A., Coffer, Paul J., Huang, Ting-T., Bos, Johannes L., Medema, Rene H., and Burgering, Boudewijn M. T.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): Geert J. P. L. Kops [1, 2]; Tobias B. Dansen [3]; Paulien E. Polderman [1]; Ingrid Saarloos [1]; Karel W. A. Wirtz [3]; Paul J. Coffer [4]; Ting-T. Huang [...]

Published
2002
Full Text
View/download PDF

33. AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1

Author

Medema, Rene H., Kops, Geert J. P. L., Bos, Johannes L., and Burgering, Boudewijn M. T.

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): René H. Medema [1, 2]; Geert J. P. L. Kops [2, 3]; Johannes L. Bos [3]; Boudewijn M. T. Burgering (corresponding author) [3] The Forkhead transcription factors AFX, FKHR [...]

Published
2000
Full Text
View/download PDF

37. MicroRNA-130a Contributes to Type-2 Classical DC-activation in Sjögren's Syndrome by Targeting Mitogen- and Stress-Activated Protein Kinase-1

Author

Lopes, Ana P., primary, van Roon, Joel A. G., additional, Blokland, Sofie L. M., additional, Wang, Maojie, additional, Chouri, Eleni, additional, Hartgring, Sarita A. Y., additional, van der Wurff-Jacobs, Kim M. G., additional, Kruize, Aike A., additional, Burgering, Boudewijn M. T., additional, Rossato, Marzia, additional, Radstake, Timothy R. D. J., additional, and Hillen, Maarten R., additional

Published
2019
Full Text
View/download PDF

38. Dysregulated miRNome of plasmacytoid dendritic cells from patients with Sjögren’s syndrome is associated with processes at the centre of their function

Author

Hillen, Maarten R, primary, Chouri, Eleni, additional, Wang, Maojie, additional, Blokland, Sofie L M, additional, Hartgring, Sarita A Y, additional, Concepcion, Arno N, additional, Kruize, Aike A, additional, Burgering, Boudewijn M T, additional, Rossato, Marzia, additional, van Roon, Joel A G, additional, and Radstake, Timothy R D J, additional

Published
2019
Full Text
View/download PDF

39. β‐catenin regulates FOXP2 transcriptional activity via multiple binding sites.

Author

Richter, Gesa, Gui, Tianshu, Bourgeois, Benjamin, Koyani, Chintan N., Ulz, Peter, Heitzer, Ellen, Lewinski, Dirk, Burgering, Boudewijn M. T., Malle, Ernst, and Madl, Tobias

Subjects
FORKHEAD transcription factors, BINDING sites, NUCLEAR magnetic resonance spectroscopy, WNT signal transduction, RNA sequencing, MOLECULAR interactions
Abstract

The transcription factor forkhead box protein P2 (FOXP2) is a highly conserved key regulator of embryonal development. The molecular mechanisms of how FOXP2 regulates embryonal development, however, remain elusive. Using RNA sequencing, we identified the Wnt signaling pathway as key target of FOXP2‐dependent transcriptional regulation. Using cell‐based assays, we show that FOXP2 transcriptional activity is regulated by the Wnt coregulator β‐catenin and that β‐catenin contacts multiple regions within FOXP2. Using nuclear magnetic resonance spectroscopy, we uncovered the molecular details of these interactions. β‐catenin contacts a disordered FOXP2 region with α‐helical propensity via its folded armadillo domain, whereas the intrinsically disordered β‐catenin N terminus and C terminus bind to the conserved FOXP2 DNA‐binding domain. Using RNA sequencing, we confirmed that β‐catenin indeed regulates transcriptional activity of FOXP2 and that the FOXP2 α‐helical motif acts as a key regulatory element of FOXP2 transcriptional activity. Taken together, our findings provide first insight into novel regulatory interactions and help to understand the intricate mechanisms of FOXP2 function and (mis)‐regulation in embryonal development and human diseases. Database: Expression data are available in the GEO database under the accession number GSE138938. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

40. Farnesoid X Receptor Activation Promotes Hepatic Amino Acid Catabolism and Ammonium Clearance in Mice

Author

Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R, Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C L, Ramos Pittol, José M, Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C M T, Verhoeven-Duif, Nanda M, Burgering, Boudewijn M T, van Mil, Saskia W C, dB&C FR-RMSC FR, and dB&C FR-RMSC FR

Subjects
Male, 0301 basic medicine, Glutamine Synthetase, Proteome, Cytoplasmic and Nuclear, Glutamine, Wistar, Gene Expression, Receptors, Cytoplasmic and Nuclear, Inbred C57BL, Mice, chemistry.chemical_compound, INT-747, Chenodeoxycholic acid, Receptors, Urea, Mice, Knockout, Bile acid, Gastroenterology, Obeticholic acid, Liver Proteome, Liver, Biochemistry, Urea cycle, Metabolome, Dietary Proteins, medicine.medical_specialty, medicine.drug_class, Knockout, Cps1, Biology, Chenodeoxycholic Acid, Bile Acids and Salts, 03 medical and health sciences, Ammonia, Internal medicine, medicine, Journal Article, Animals, Rats, Wistar, Liver X receptor, Hepatology, Catabolism, Rats, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, Hepatocytes, Farnesoid X receptor
Abstract

Background & Aims The nuclear receptor subfamily 1 group H member 4 (NR1H4 or farnesoid X receptor [FXR]) regulates bile acid synthesis, transport, and catabolism. FXR also regulates postprandial lipid and glucose metabolism. We performed quantitative proteomic analyses of liver tissues from mice to evaluate these functions and investigate whether FXR regulates amino acid metabolism. Methods To study the role of FXR in mouse liver, we used mice with a disruption of Nr1h4 (FXR-knockout mice) and compared them with floxed control mice. Mice were gavaged with the FXR agonist obeticholic acid or vehicle for 11 days. Proteome analyses, as well as targeted metabolomics and chromatin immunoprecipitation, were performed on the livers of these mice. Primary rat hepatocytes were used to validate the role of FXR in amino acid catabolism by gene expression and metabolomics studies. Finally, control mice and mice with liver-specific disruption of Nr1h4 (liver FXR-knockout mice) were re-fed with a high-protein diet after 6 hours fasting and gavaged a 15 NH 4 Cl tracer. Gene expression and the metabolome were studied in the livers and plasma from these mice. Results In livers of control mice and primary rat hepatocytes, activation of FXR with obeticholic acid increased expression of proteins that regulate amino acid degradation, ureagenesis, and glutamine synthesis. We found FXR to bind to regulatory sites of genes encoding these proteins in control livers. Liver tissues from FXR-knockout mice had reduced expression of urea cycle proteins, and accumulated precursors of ureagenesis, compared with control mice. In liver FXR-knockout mice on a high-protein diet, the plasma concentration of newly formed urea was significantly decreased compared with controls. In addition, liver FXR-knockout mice had reduced hepatic expression of enzymes that regulate ammonium detoxification compared with controls. In contrast, obeticholic acid increased expression of genes encoding enzymes involved in ureagenesis compared with vehicle in C57Bl/6 mice. Conclusions In livers of mice, FXR regulates amino acid catabolism and detoxification of ammonium via ureagenesis and glutamine synthesis. Failure of the urea cycle and hyperammonemia are common in patients with acute and chronic liver diseases; compounds that activate FXR might promote ammonium clearance in these patients.

Published
2017

42. Interplay between metabolic identities in the intestinal crypt supports stem cell function

Author

Rodríguez-Colman, Maria J, Schewe, Matthias, Meerlo, Maaike, Stigter, Edwin, Gerrits, Johan, Pras-Raves, Mia, Sacchetti, Andrea, Hornsveld, Marten, Oost, Koen C, Snippert, Hugo J, Verhoeven-Duif, Nanda, Fodde, Riccardo, Burgering, Boudewijn M T, Rodríguez-Colman, Maria J, Schewe, Matthias, Meerlo, Maaike, Stigter, Edwin, Gerrits, Johan, Pras-Raves, Mia, Sacchetti, Andrea, Hornsveld, Marten, Oost, Koen C, Snippert, Hugo J, Verhoeven-Duif, Nanda, Fodde, Riccardo, and Burgering, Boudewijn M T

Published
2017

44. Farnesoid X Receptor Activation Promotes Hepatic Amino Acid Catabolism and Ammonium Clearance in Mice

Author

dB&C FR-RMSC FR, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R, Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C L, Ramos Pittol, José M, Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C M T, Verhoeven-Duif, Nanda M, Burgering, Boudewijn M T, van Mil, Saskia W C, dB&C FR-RMSC FR, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R, Ramos, Rúben J J, Gerrits, Johan, Willemsen, Ellen C L, Ramos Pittol, José M, Ijssennagger, Noortje, Houweling, Martin, Prinsen, Hubertus C M T, Verhoeven-Duif, Nanda M, Burgering, Boudewijn M T, and van Mil, Saskia W C

Published
2017

45. Quantitative liver proteomics identifies FGF19 targets that couple metabolism and proliferation

Author

CMM, UMC Utrecht, CMM Groep Van Mil, Child Health, CMM Groep Burgering, Cancer, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R., Burgering, Boudewijn M T, Van Mil, Saskia W C, CMM, UMC Utrecht, CMM Groep Van Mil, Child Health, CMM Groep Burgering, Cancer, Massafra, Vittoria, Milona, Alexandra, Vos, Harmjan R., Burgering, Boudewijn M T, and Van Mil, Saskia W C

Published
2017

46. Interplay between metabolic identities in the intestinal crypt supports stem cell function

Author

CMM Groep Burgering, Cancer, Genetica Sectie Metabole Diagnostiek, Child Health, CMM Groep Snippert, CMM Sectie Molecular Cancer Research, CMM, Rodríguez-Colman, Maria J, Schewe, Matthias, Meerlo, Maaike, Stigter, Edwin, Gerrits, Johan, Pras-Raves, Mia, Sacchetti, Andrea, Hornsveld, Marten, Oost, Koen C, Snippert, Hugo J, Verhoeven-Duif, Nanda, Fodde, Riccardo, Burgering, Boudewijn M T, CMM Groep Burgering, Cancer, Genetica Sectie Metabole Diagnostiek, Child Health, CMM Groep Snippert, CMM Sectie Molecular Cancer Research, CMM, Rodríguez-Colman, Maria J, Schewe, Matthias, Meerlo, Maaike, Stigter, Edwin, Gerrits, Johan, Pras-Raves, Mia, Sacchetti, Andrea, Hornsveld, Marten, Oost, Koen C, Snippert, Hugo J, Verhoeven-Duif, Nanda, Fodde, Riccardo, and Burgering, Boudewijn M T

Published
2017

48. Proteome-wide Changes in Protein Turnover Rates in C. elegans Models of Longevity and Age-Related Disease

Author

Visscher, Marieke, De Henau, Sasha, Wildschut, Mattheus H E, van Es, Robert M., Dhondt, Ineke, Michels, Helen, Kemmeren, Patrick, Nollen, Ellen A., Braeckman, Bart P., Burgering, Boudewijn M T, Vos, Harmjan R., Dansen, Tobias B., Visscher, Marieke, De Henau, Sasha, Wildschut, Mattheus H E, van Es, Robert M., Dhondt, Ineke, Michels, Helen, Kemmeren, Patrick, Nollen, Ellen A., Braeckman, Bart P., Burgering, Boudewijn M T, Vos, Harmjan R., and Dansen, Tobias B.

Published
2016

49. The small GTPase RALA controls c-Jun N-terminal kinase-mediated FOXO activation by regulation of a JIP1 scaffold complex

Author

van den Berg, Maaike C W, van Gogh, Inkie J A, Smits, Alida M M, van Triest, Miranda, Dansen, Tobias B, Visscher, Marieke, Polderman, Paulien E, Vliem, Marjolein J, Rehmann, Holger, Burgering, Boudewijn M T, van den Berg, Maaike C W, van Gogh, Inkie J A, Smits, Alida M M, van Triest, Miranda, Dansen, Tobias B, Visscher, Marieke, Polderman, Paulien E, Vliem, Marjolein J, Rehmann, Holger, and Burgering, Boudewijn M T

Published
2016

50. Proteome-wide Changes in Protein Turnover Rates in C. elegans Models of Longevity and Age-Related Disease

Author

CMM, UMC Utrecht, CMM Groep Burgering, CMM Groep Dansen, Cancer, Groep Holstege, CMM Sectie Molecular Cancer Research, Visscher, Marieke, De Henau, Sasha, Wildschut, Mattheus H E, van Es, Robert M., Dhondt, Ineke, Michels, Helen, Kemmeren, Patrick, Nollen, Ellen A., Braeckman, Bart P., Burgering, Boudewijn M T, Vos, Harmjan R., Dansen, Tobias B., CMM, UMC Utrecht, CMM Groep Burgering, CMM Groep Dansen, Cancer, Groep Holstege, CMM Sectie Molecular Cancer Research, Visscher, Marieke, De Henau, Sasha, Wildschut, Mattheus H E, van Es, Robert M., Dhondt, Ineke, Michels, Helen, Kemmeren, Patrick, Nollen, Ellen A., Braeckman, Bart P., Burgering, Boudewijn M T, Vos, Harmjan R., and Dansen, Tobias B.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results